1,721,531 research outputs found

    The role of group I metabotropic glutamate receptors in absence epilepsy

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    Contains fulltext : 157139.pdf (Publisher’s version ) (Open Access)RU Radboud Universiteit, 08 juni 2016Promotores : Luijtelaar, E.L.J.M. van, Nicoletti, F. Co-promotores : Rijn, C.M. van, Ngomba, R.T.229 p

    Different generations of type-b monoamine oxidase inhibitors in parkinson’s disease: From bench to bedside

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    Three inhibitors of type-B monoamine oxidase (MAOB), selegiline, rasagiline, and safinamide, are used for the treatment of Parkinson’s disease (PD). All three drugs improve motor signs of PD, and are effective in reducing motor fluctuations in patients undergoing long-term L-DOPA treatment. The effect of MAOB inhibitors on non-motor symptoms is not uniform and may not be class-related. Selegiline and rasagiline are irreversible inhibitors forming a covalent bond within the active site of MAOB. In contrast, safinamide is a reversible MAOB inhibitor, and also inhibits volt-age-sensitive sodium channels and glutamate release. Safinamide is the prototype of a new generation of multi-active MAOB inhibitors, which includes the antiepileptic drug, zonisamide. Inhibition of MAOB-mediated dopamine metabolism largely accounts for the antiparkinsonian effect of the three drugs. Dopamine metabolism by MAOB generates reactive oxygen species, which contribute to nigro-striatal degeneration. Among all antiparkinsonian agents, MAOB inhibitors are those with the greatest neuroprotective potential because of inhibition of dopamine metabolism, induction of neurotrophic factors, and, in the case of safinamide, inhibition of glutamate release. The recent development of new experimental animal models that more closely mimic the progressive neurodegeneration associated with PD will allow to test the hypothesis that MAOB inhibitors may slow the progression of PD

    Metabotropic glutamate 1 receptor: Current concepts and perspectives

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    Almost 25 years after the first report that glutamate can activate receptors coupled to heterotrimeric G-proteins, tremendous progress has been made in the field of metabotropic glutamate receptors. Now, eight members of this family of glutamate receptors, encoded by eight different genes that share distinctive structural features have been identified. The first cloned receptor, the metabotropic glutamate (mGlu) receptor mGlu1 has probably been the most extensively studied mGlu receptor, and in many respects it represents a prototypical subtype for this family of receptors. Its biochemical, anatomical, physiological, and pharmacological characteristics have been intensely investigated. Together with subtype 5, mGlu1 receptors constitute a subgroup of receptors that couple to phospholipase C and mobilize Ca2+ from intracellular stores. Several alternatively spliced variants of mGlu1 receptors, which differ primarily in the length of their C-terminal domain and anatomical localization, have been reported. Use of a number of genetic approaches and the recent development of selective antagonists have provided a means for clarifying the role played by this receptor in a number of neuronal systems. In this article we discuss recent advancements in the pharmacology and concepts about the intracellular transduction and pathophysiological role of mGlu1 receptors and review earlier data in view of these novel findings. The impact that this new and better understanding of the specific role of these receptors may have on novel treatment strategies for a variety of neurological and psychiatric disorders is considered. Copyright © 2008 by The American Society for Pharmacology and Experimental Therapeutics

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Resoconto preliminare degli scavi dellinsediamento di Mursia (Pantelleria)

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    Gli scavi nell’abitato dell’età del Bronzo di Mursia hanno esplorato sia il promontorio sia il settore orientale (la c.d acropoli) mettendo in luce numerosi edifici distinti in tre fasi. In una prima fase si sviluppano capanne seminterrate dal perimetro ovale molto allungato con una abside pseudo-appuntita e l’altra semicircolare. Nella fase più recente compaiono strutture di forma circolare o quadrangolare, spesso agglutinate in più ambienti. Gli scavi consentono di ricostruire un quadro sulle dinamiche insediamentali e sulle tipologie strutturali. Le datazioni radiometriche collocano l’abitato nella prima metà del II millennio a.C

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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